Boron-containing compounds

Abstract

Described herein are boron-containing compounds, compositions, and methods for their preparation.

What is claimed is: 
     
       1. A continuous flow process for making a compound of Formula (III): 
       
         
           
           
               
               
           
         
         wherein 
         P 1  is a hydroxyl protecting group; and 
         P 2  is a carboxyl protecting group; 
         the process comprising: 
         (a) providing a first continuous flow of a compound of Formula (II) and dichloromethane: 
       
       
         
           
           
               
               
           
         
         (b) providing a second continuous flow of a base selected from lithium diisopropylamide and 2,2,6,6-tetramethylpiperidinylmagnesium chloride:lithium chloride; 
         (c) mixing the first continuous flow and the second continuous flow in a mixing chamber to yield a third continuous flow comprising a first reactive intermediate; 
         (d) collecting the first reactive intermediate into a collection vessel at the output of the third continuous flow; 
         (e) treating the first reactive intermediate with a Lewis acid; and 
         (f) warming the collection vessel to provide the compound of Formula (III). 
       
     
     
       2. The process of  claim 1 , wherein the first continuous flow further comprises a coordinating ethereal solvent and the second continuous flow further comprises a coordinating ethereal solvent. 
     
     
       3. The process of  claim 1 , wherein the second continuous flow further comprises heptane, ethyl benzene, or a combination thereof. 
     
     
       4. The process of  claim 1 , wherein the Lewis acid is provided as a fourth continuous flow further comprising a coordinating ethereal solvent. 
     
     
       5. The process of  claim 1 , wherein the water content of the coordinating ethereal solvent is less than about 0.08% (w/w), less than about 0.05% (w/w), or the coordinating ethereal solvent is substantially free of water. 
     
     
       6. The process of  claim 1 , wherein the dichloromethane is substantially free of water. 
     
     
       7. The process of  claim 1 , wherein the base is substantially free of water. 
     
     
       8. The process of  claim 3 , wherein the heptane, ethyl benzene, or a combination thereof is substantially free of water. 
     
     
       9. The process of  claim 1 , comprising pre-cooling the first continuous flow to a temperature in the range of about −40° C. to about −10° C. and pre-cooling the second continuous flow to a temperature in the range of about −40° C. to about −10° C. 
     
     
       10. The process of  claim 1 , wherein the third continuous flow has a temperature in the range of about −20° C. to about +10° C. 
     
     
       11. The process of  claim 1 , comprising maintaining the collection vessel at the output of the third continuous flow at a temperature in the range of about −10° C. to about +10° C. 
     
     
       12. The process of  claim 1 , wherein the collection vessel is warmed to room temperature in step (f). 
     
     
       13. The process of  claim 1 , wherein the molar ratio of the base to a compound of Formula (II) is in the range of about 1:1 to about 1.5:1, the molar ratio of the dichloromethane to a compound of Formula (II) is in the range of about 5:1 and 7:1, and the molar ratio of the Lewis acid to a compound of Formula (II) is in the range of about 1:1 and 3:1. 
     
     
       14. The process of  claim 1 , wherein the base is lithium diisopropylamide and the Lewis acid is ZnCl 2 . 
     
     
       15. The process of  claim 1 , wherein P 1  is methyl and P 2  is tert-butyl.